Discovery of New Proxyphylline-Based Chiral Cocrystals: Solid State Landscape and Dehydration Mechanism
journal contributionposted on 15.05.2020, 20:09 by Lina C. Harfouche, Nicolas Couvrat, Morgane Sanselme, Clément Brandel, Yohann Cartigny, Samuel Petit, Gérard Coquerel
A cocrystal screening of the chiral drug “proxyphylline” (PXL) and achiral coformers was performed using dry or solvent assisted grinding and evaporation methods, yielding 10 different original solid forms with a 1:1 stoichiometry. Among them, three anhydrous cocrystals and a monohydrated conglomerate forming system have been identified with salicylic acid (SA). The crystal structures of the monohydrate and one of the racemic anhydrous forms were determined by X-ray single crystal experiments. The dehydration mechanism of the hydrate has been investigated by thermal analysis, X-ray powder diffraction, and water sorption–desorption cycles. The importance of water molecules in the crystal structure and the concomitant loss of both water and SA (cocrystal former) during the dehydration suggest a destructive mechanism.